NZ242546A - Phosphono substituted dipeptide derivatives and pharmaceutical compositions - Google Patents

Info

Publication number

NZ242546A

NZ242546A NZ242546A NZ24254692A NZ242546A NZ 242546 A NZ242546 A NZ 242546A NZ 242546 A NZ242546 A NZ 242546A NZ 24254692 A NZ24254692 A NZ 24254692A NZ 242546 A NZ242546 A NZ 242546A

Authority

NZ

New Zealand

Prior art keywords

pharmaceutically acceptable

propionyl

acceptable salt

biphenylyl

phosphonomethylamino

Prior art date

1991-05-01

Links

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• Global Dossier
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• 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 title claims description 13
• 108010016626 Dipeptides Proteins 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims description 165
• 150000003839 salts Chemical class 0.000 claims description 156
• -1 6-tetrahydronaphthyl Chemical group 0.000 claims description 127
• 125000000217 alkyl group Chemical group 0.000 claims description 108
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 65
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 58
• 238000000034 method Methods 0.000 claims description 49
• 101100295738 Gallus gallus COR3 gene Proteins 0.000 claims description 47
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 45
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
• 229910052739 hydrogen Inorganic materials 0.000 claims description 43
• 239000001257 hydrogen Substances 0.000 claims description 42
• 239000000203 mixture Substances 0.000 claims description 37
• 150000002148 esters Chemical class 0.000 claims description 34
• 125000003545 alkoxy group Chemical group 0.000 claims description 30
• 150000002431 hydrogen Chemical class 0.000 claims description 30
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
• 239000002253 acid Substances 0.000 claims description 27
• 229910052736 halogen Inorganic materials 0.000 claims description 26
• 150000002367 halogens Chemical class 0.000 claims description 26
• 229910052701 rubidium Inorganic materials 0.000 claims description 20
• 102000003729 Neprilysin Human genes 0.000 claims description 19
• 108090000028 Neprilysin Proteins 0.000 claims description 19
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
• 230000008569 process Effects 0.000 claims description 18
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
• 238000002360 preparation method Methods 0.000 claims description 17
• 150000001408 amides Chemical class 0.000 claims description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
• 125000004423 acyloxy group Chemical group 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 13
• 125000003282 alkyl amino group Chemical group 0.000 claims description 13
• 229910052708 sodium Inorganic materials 0.000 claims description 12
• 239000011734 sodium Substances 0.000 claims description 12
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 11
• 125000002947 alkylene group Chemical group 0.000 claims description 11
• 125000003118 aryl group Chemical group 0.000 claims description 11
• 125000002837 carbocyclic group Chemical group 0.000 claims description 11
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
• 229940002612 prodrug Drugs 0.000 claims description 11
• 239000000651 prodrug Substances 0.000 claims description 11
• 125000002541 furyl group Chemical group 0.000 claims description 10
• 229910052705 radium Inorganic materials 0.000 claims description 10
• 125000001544 thienyl group Chemical group 0.000 claims description 10
• 150000005690 diesters Chemical class 0.000 claims description 9
• 125000006239 protecting group Chemical group 0.000 claims description 9
• JTQWXNZXTRVPHN-LJAQVGFWSA-N 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)NCCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 JTQWXNZXTRVPHN-LJAQVGFWSA-N 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
• 230000005764 inhibitory process Effects 0.000 claims description 8
• 125000001624 naphthyl group Chemical group 0.000 claims description 8
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 125000001424 substituent group Chemical group 0.000 claims description 8
• 125000005042 acyloxymethyl group Chemical group 0.000 claims description 7
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
• 230000003287 optical effect Effects 0.000 claims description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 5
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000000524 functional group Chemical group 0.000 claims description 5
• 125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims description 4
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• MVRLTBIHUWUGAR-KRWDZBQOSA-N 3-[[(2s)-3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]propanoic acid Chemical compound C1=CC(C[C@@H](C(=O)NCCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=CC=C1 MVRLTBIHUWUGAR-KRWDZBQOSA-N 0.000 claims description 4
• 229960003767 alanine Drugs 0.000 claims description 4
• WDXHEDSUUDLQKV-BHVANESWSA-N benzyl 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)NCCC(=O)OCC=1C=CC=CC=1)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 WDXHEDSUUDLQKV-BHVANESWSA-N 0.000 claims description 4
• 125000004956 cyclohexylene group Chemical group 0.000 claims description 4
• 230000002401 inhibitory effect Effects 0.000 claims description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
• 229920002472 Starch Polymers 0.000 claims description 3
• 230000002378 acidificating effect Effects 0.000 claims description 3
• 239000002775 capsule Substances 0.000 claims description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
• GTTBQSNGUYHPNK-UHFFFAOYSA-N hydroxymethylphosphonic acid Chemical class OCP(O)(O)=O GTTBQSNGUYHPNK-UHFFFAOYSA-N 0.000 claims description 3
• 239000008101 lactose Substances 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 235000019698 starch Nutrition 0.000 claims description 3
• YEPZOYCLNPHLRE-MHZLTWQESA-N (4-acetamidophenoxy)-[[[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl]phosphinic acid Chemical compound C(C)(=O)NC1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1 YEPZOYCLNPHLRE-MHZLTWQESA-N 0.000 claims description 2
• DHCDIFCDUYITKF-LHEWISCISA-N 2,3-dihydro-1h-inden-5-yl 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)NCCC(=O)OC=1C=C2CCCC2=CC=1)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 DHCDIFCDUYITKF-LHEWISCISA-N 0.000 claims description 2
• MFCBQBHMDPFEHT-NDEPHWFRSA-N 2-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]acetic acid Chemical compound C([C@@H](C(=O)NCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 MFCBQBHMDPFEHT-NDEPHWFRSA-N 0.000 claims description 2
• RCGSYJNOCWJPHN-UHFFFAOYSA-N 2-[[3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]acetic acid Chemical compound C1=CC(CC(C(=O)NCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=CC=C1 RCGSYJNOCWJPHN-UHFFFAOYSA-N 0.000 claims description 2
• IEWZJBRCSADZCC-IBGZPJMESA-N 3-[[(2s)-2-(dimethoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C1=CC(C[C@H](NCP(=O)(OC)OC)C(=O)NCCC(O)=O)=CC=C1C1=CC=CC=C1 IEWZJBRCSADZCC-IBGZPJMESA-N 0.000 claims description 2
• KQQQDEPAGWLQFV-QHCPKHFHSA-N 3-[[(2s)-2-[[hydroxy(phenoxy)phosphoryl]methylamino]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)NCCC(=O)O)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 KQQQDEPAGWLQFV-QHCPKHFHSA-N 0.000 claims description 2
• SSZAYSZFMOTRGA-XIFFEERXSA-N 3-[[(2s)-2-[bis(4-acetamidophenoxy)phosphorylmethylamino]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C1=CC(NC(=O)C)=CC=C1OP(=O)(OC=1C=CC(NC(C)=O)=CC=1)CN[C@H](C(=O)NCCC(O)=O)CC1=CC=C(C=2C=CC=CC=2)C=C1 SSZAYSZFMOTRGA-XIFFEERXSA-N 0.000 claims description 2
• RMTSQBXDRRSABG-DHUJRADRSA-N 3-[[(2s)-2-[bis(4-propylphenoxy)phosphorylmethylamino]-3-(4-phenylphenyl)propanoyl]amino]propanoic acid Chemical compound C1=CC(CCC)=CC=C1OP(=O)(OC=1C=CC(CCC)=CC=1)CN[C@H](C(=O)NCCC(O)=O)CC1=CC=C(C=2C=CC=CC=2)C=C1 RMTSQBXDRRSABG-DHUJRADRSA-N 0.000 claims description 2
• KFHKPFNUGLOSDB-LJAQVGFWSA-N 3-[[(2s)-3-[4-(4-chlorophenyl)phenyl]-2-(diphenoxyphosphorylmethylamino)propanoyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)NCCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 KFHKPFNUGLOSDB-LJAQVGFWSA-N 0.000 claims description 2
• SUDHZUVTDLPZRS-UHFFFAOYSA-N 3-[[3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]propanoic acid;hydrobromide Chemical compound Br.C1=CC(CC(C(=O)NCCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=CC=C1 SUDHZUVTDLPZRS-UHFFFAOYSA-N 0.000 claims description 2
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
• XMLNCVHLDPWKCQ-PMERELPUSA-N 4-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]butanoic acid Chemical compound C([C@@H](C(=O)NCCCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 XMLNCVHLDPWKCQ-PMERELPUSA-N 0.000 claims description 2
• IYBXNSMBKTWFHQ-NXFUPXHFSA-N 4-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1NC(=O)[C@@H](NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)CC1=CC=C(C=2C=CC=CC=2)C=C1 IYBXNSMBKTWFHQ-NXFUPXHFSA-N 0.000 claims description 2
• XUSIYPQRLSSLNV-UHFFFAOYSA-N 4-[[3-(4-phenylphenyl)-2-(phosphonomethylamino)propanoyl]amino]butanoic acid Chemical compound C1=CC(CC(C(=O)NCCCC(=O)O)NCP(O)(O)=O)=CC=C1C1=CC=CC=C1 XUSIYPQRLSSLNV-UHFFFAOYSA-N 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
• MEZULCFJPPZDTE-XIFFEERXSA-N 7-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]heptanoic acid Chemical compound C([C@@H](C(=O)NCCCCCCC(=O)O)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 MEZULCFJPPZDTE-XIFFEERXSA-N 0.000 claims description 2
• FPHSLIJVXMWQJC-NDEPHWFRSA-N C([C@@H](C(=O)NCCC(=O)OCC)N(CP(O)(O)=O)C=1C=C2CCCC2=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 Chemical compound C([C@@H](C(=O)NCCC(=O)OCC)N(CP(O)(O)=O)C=1C=C2CCCC2=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 FPHSLIJVXMWQJC-NDEPHWFRSA-N 0.000 claims description 2
• KEQQJVLAVSYZHZ-LHEWISCISA-N C1=CC(OC)=CC=C1OP(=O)(OC=1C=CC(OC)=CC=1)CN[C@H](C(=O)NCCC(=O)OCC=1C=CC=CC=1)CC1=CC=C(C=2C=CC=CC=2)C=C1 Chemical compound C1=CC(OC)=CC=C1OP(=O)(OC=1C=CC(OC)=CC=1)CN[C@H](C(=O)NCCC(=O)OCC=1C=CC=CC=1)CC1=CC=C(C=2C=CC=CC=2)C=C1 KEQQJVLAVSYZHZ-LHEWISCISA-N 0.000 claims description 2
• XEUJBBIFTMMOCB-HKBQPEDESA-N COC1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC1=CC=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1 Chemical compound COC1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC1=CC=CC=C1)CC1=CC=C(C=C1)C1=CC=CC=C1 XEUJBBIFTMMOCB-HKBQPEDESA-N 0.000 claims description 2
• GTWHAYLSQWREFO-SANMLTNESA-N COC=1C=C(C=CC1)N([C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1)CP(=O)(O)O Chemical compound COC=1C=C(C=CC1)N([C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1)CP(=O)(O)O GTWHAYLSQWREFO-SANMLTNESA-N 0.000 claims description 2
• 239000004471 Glycine Substances 0.000 claims description 2
• QMLWZEZYGODKAQ-BHVANESWSA-N [2-(diethylamino)-2-oxoethyl] 3-[[(2S)-2-[bis(3-methoxyphenoxy)phosphorylmethylamino]-3-(4-phenylphenyl)propanoyl]amino]propanoate Chemical compound COC=1C=C(C=CC1)OP(=O)(OC1=CC(=CC=C1)OC)CN[C@H](C(=O)NCCC(=O)OCC(N(CC)CC)=O)CC1=CC=C(C=C1)C1=CC=CC=C1 QMLWZEZYGODKAQ-BHVANESWSA-N 0.000 claims description 2
• POAXRLIGJNLEFJ-SANMLTNESA-N [[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-(4-methylphenoxy)phosphinic acid Chemical compound CC1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1 POAXRLIGJNLEFJ-SANMLTNESA-N 0.000 claims description 2
• UUISNSYMVJLWRI-NDEPHWFRSA-N [[(2S)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-(4-propan-2-ylphenoxy)phosphinic acid Chemical compound C(C)(C)C1=CC=C(C=C1)OP(=O)(O)CN[C@H](C(=O)NCCC(=O)OCC)CC1=CC=C(C=C1)C1=CC=CC=C1 UUISNSYMVJLWRI-NDEPHWFRSA-N 0.000 claims description 2
• JUSLIBLEBQFXHK-NDEPHWFRSA-N [[(2s)-1-(4-methoxycarbonylanilino)-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C1=CC(C(=O)OC)=CC=C1NC(=O)[C@@H](NCP(O)(=O)OC=1C=CC=CC=1)CC1=CC=C(C=2C=CC=CC=2)C=C1 JUSLIBLEBQFXHK-NDEPHWFRSA-N 0.000 claims description 2
• UWJVDOOSSQISRC-VWLOTQADSA-N [[(2s)-1-[(3-ethoxy-3-oxopropyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@@H](C(=O)NCCC(=O)OCC)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 UWJVDOOSSQISRC-VWLOTQADSA-N 0.000 claims description 2
• UQBLGLVSPFTLIG-DMVZSUBZSA-N [[(2s)-1-[(4-ethoxycarbonylcyclohexyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C1CC(C(=O)OCC)CCC1NC(=O)[C@@H](NCP(O)(=O)OC=1C=CC=CC=1)CC1=CC=C(C=2C=CC=CC=2)C=C1 UQBLGLVSPFTLIG-DMVZSUBZSA-N 0.000 claims description 2
• XEYDGCVRBXPKTF-LJAQVGFWSA-N [[(2s)-1-[(7-ethoxy-7-oxoheptyl)amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@@H](C(=O)NCCCCCCC(=O)OCC)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 XEYDGCVRBXPKTF-LJAQVGFWSA-N 0.000 claims description 2
• UTHFQNVANYBPJU-YTTGMZPUSA-N [[(2s)-1-[[3-(2,3-dihydro-1h-inden-5-yloxy)-3-oxopropyl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@H](NCP(=O)(O)OC=1C=CC=CC=1)C(=O)NCCC(=O)OC=1C=C2CCCC2=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 UTHFQNVANYBPJU-YTTGMZPUSA-N 0.000 claims description 2
• YKKZHAROJOALLS-NDEPHWFRSA-N [[(2s)-1-[[3-[2-(diethylamino)-2-oxoethoxy]-3-oxopropyl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@@H](C(=O)NCCC(=O)OCC(=O)N(CC)CC)NCP(O)(=O)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 YKKZHAROJOALLS-NDEPHWFRSA-N 0.000 claims description 2
• HHDKPTVOIUHECP-PMERELPUSA-N [[(2s)-1-oxo-1-[(3-oxo-3-phenylmethoxypropyl)amino]-3-(4-phenylphenyl)propan-2-yl]amino]methyl-phenoxyphosphinic acid Chemical compound C([C@H](NCP(=O)(O)OC=1C=CC=CC=1)C(=O)NCCC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 HHDKPTVOIUHECP-PMERELPUSA-N 0.000 claims description 2
• AXESDPRCBYMGGU-UHFFFAOYSA-N [[1-oxo-1-[(3-oxo-3-phenylmethoxypropyl)amino]-3-(4-phenylphenyl)propan-2-yl]amino]methylphosphonic acid Chemical compound C=1C=CC=CC=1COC(=O)CCNC(=O)C(NCP(O)(=O)O)CC(C=C1)=CC=C1C1=CC=CC=C1 AXESDPRCBYMGGU-UHFFFAOYSA-N 0.000 claims description 2
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• 239000003814 drug Substances 0.000 claims description 2
• VMIRRWHXJUNWKE-HKBQPEDESA-N ethyl 3-[[(2s)-2-(diphenoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)NCCC(=O)OCC)NCP(=O)(OC=1C=CC=CC=1)OC=1C=CC=CC=1)C(C=C1)=CC=C1C1=CC=CC=C1 VMIRRWHXJUNWKE-HKBQPEDESA-N 0.000 claims description 2
• 239000007903 gelatin capsule Substances 0.000 claims description 2
• 230000002452 interceptive effect Effects 0.000 claims description 2
• 235000019359 magnesium stearate Nutrition 0.000 claims description 2
• 239000000843 powder Substances 0.000 claims description 2
• 239000008107 starch Substances 0.000 claims description 2
• 150000005691 triesters Chemical class 0.000 claims description 2
• UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims 3
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